Among the complement proteins the ninth component (C9) has the unprecedented property to form linear homopolymers (poly-C9) upon incubation with detergents or chaotropic agents. C9 polymerization, in all probability, is the key to its cytolytic function and its analysis is the subject of this proposal. The long range objectives of this work are two-fold: 1) To elaborate a test system using isolated poly-C9 and single bilayer phospholipid vesicles that allows the molecular analysis of the cytolytic mechanism in a simple model reaction. 2) To determine to which extent poly-C9 mediated reactions are representative for reactions of C9 as subunit of the C5b-9 complex. For this purpose the following specific projects will be pursued: 1) Analysis of the molecular mechanism of C9 polymerization and of its interaction with lipid bilayers. 2) Mapping of specific sites on C9 polymers by chemical and ultrastructural techniques. 3) Investigation of the interaction of isolated C8 with poly-C9 and the effect of this complex on artificial membranes. 4) Determiation of C9 multiplicity and C9-C9 interaction within the C5b-9 complex. 5) Analysis of the relation of C8:C9 ratios on the ultrastructure and on the state of aggregation of the C5b-9 complex. Ultimately, the molecular analysis of interactions of C9 with itself and with C8 are expected to further the understanding of complement mediated cytolysis.